Polypoid endobronchial Hodgkin lymphoma with an initial response to photodynamic therapy

Endobronchial presentation of Hodgkin lymphoma is rare and can be confused clinically and radiographically with pulmonary small cell carcinoma. We present a case of an obstructive endobronchial presentation of nodular sclerosing classic Hodgkin lymphoma, initially misdiagnosed as small cell carcinoma, with endobronchial vasculitis and associated hemoptysis. Photodynamic therapy relieved the obstruction before induction of tumor-specific therapy. This case demonstrates the successful use of photodynamic therapy in obstructive endobronchial Hodgkin lymphoma.     

Composite Hodgkin lymphoma and mantle cell lymphoma: two clonally unrelated tumors

Association of Hodgkin lymphoma and non-Hodgkin lymphoma is rare and, specifically, the combination of Hodgkin lymphoma and mantle cell lymphoma has not been previously described. Here we describe composite mantle cell lymphoma and Hodgkin lymphoma affecting the spleen in one case and the eyelid and cervical lymph nodes in a second. In both, nodules of classical Hodgkin lymphoma were intermixed with diffuse or nodular areas of typical mantle cell lymphoma. Immunohistochemical and molecular analyses confirmed cyclin D1 overexpression secondary to the translocation t(11;14) in the small mantle cell lymphoma component; with CD30, CD15, and EBV expression in the Hodgkin and Reed-Sternberg cells. Finally, clonal analysis of rearranged immunoglobulin genes performed on microdissected Hodgkin and Reed-Sternberg and mantle cell lymphoma cells provided definite evidence of separate clonal origins of the two tumors in the patients. These EBV-positive, clonally unrelated tumors seem to represent true composite neoplasms, in contrast to cases showing merely clonal progression.     

Unique collision of hodgkin lymphoma and adenosquamous carcinoma in the uterine cervix: synchronous malignant neoplasms of the cervix

To document the first reported synchronous occurrence of Hodgkin lymphoma and adenosquamous carcinoma involving the female genital tract. Review of cytologic, histologic, and immunohistochemical studies obtained from a 50-year-old, multiparous, postmenopausal, Hispanic female who had a left inguinal mass, bilateral lower extremity pain and numbness, fatigue, anorexia, a 20- to 30-pound weight loss, and a malodorous vaginal discharge at presentation is presented. Cervical squamous cell carcinoma was diagnosed by routine cytologic and histologic analysis. Hodgkin lymphoma subsequently was diagnosed in the inguinal lymph nodes by fine-needle aspiration biopsy and excisional biopsy before the patient underwent hysterectomy. In addition to invasive and in situ adenosquamous carcinoma of the uterine cervix, the hysterectomy specimen also contained previously unsuspected Hodgkin lymphoma. To our knowledge, this is the first reported case of adenosquamous carcinoma and Hodgkin lymphoma synchronously involving the female reproductive tract.     

Ten cases of rare breast tumors. Review and surgical management]

Ten cases of rare breast tumors are reported along with review of the literature. Three of the patients had cystosarcoma phylloides, one a primary carcinoid of the breast, two metastasis to the breast (bronchus carcinoma and carcinoma of the maxillary sinus), two malignant lymphoma and two Hodgkin lymphoma of the breast. We present a discussion of diagnostic and therapeutic procedures of breast tumors. Specially in rare breast tumors an exact histological diagnosis is important in order to avoid unnecessary surgical treatment and to guide further therapy.     

肾原发性淋巴瘤二例报告并文献复习

目的探讨肾脏原发性恶性淋巴瘤的临床病理特点、影像学特征及诊治。方法总结2例肾脏原发性淋巴瘤患者的临床病理、影像学特点、诊断、鉴别诊断及治疗预后资料,并结合文献复习讨论。结果2例患者均为中老年人,发病后均有腰部隐痛或钝痛;影像学检查均显示肾脏占位性病变;病理诊断均为肾脏原发性恶性淋巴瘤,其中1例为霍奇金淋巴瘤（以结节硬化型为主）,1例为非霍奇金淋巴瘤（B细胞性）。1例行手术加化疗,1例单纯化疗;患者预后佳,目前分别存活1年和5年8个月。结论肾脏原发性恶性淋巴瘤十分罕见,尤其是霍奇金淋巴瘤;确诊需病理组织学检查,治疗主要是单纯化疗或根治性肾切除加化疗。     

Obstruction respiratoire peranesthésique en cas de lymphome malin médiastinal

Three cases of asphyxia at the beginning of general anaesthesia for mediastinoscopy or biopsy of adenopathy are described in patients with malignant lymphoma. One of them died in spite of endobronchial intubation, artificial ventilation and steroids. The two others recovered when specific chemotherapy was added to the same symptomatic treatment. The risk of respiratory obstruction seems higher in non-Hodgkin than in Hodgkin lymphomas. This kind of obstruction is not relieved by an antiasthmatic therapy. Pulmonary lymphatic filtration may be hindered in case of mediastinal lymphoma, especially during anaesthetic induction, and pulmonary interstitial congestion may occur impeding gas propagation. Specific chemotherapy according to the histological type of the tumour may relieve the compression and respiratory obstruction in a few hours.     

结直肠非霍奇金淋巴瘤30例分析

目的 探讨结直肠非霍奇金淋巴瘤的临床特点、诊治及预后.方法 回顾性分析1990年1月至2009年12月收治的30例结直肠非霍奇金淋巴瘤的临床资料,应用Kaplan-Meier法、LogRank检验对其进行单因素生存预后分析.结果 肿瘤大小、有无远处转移和治疗方式是影响病人预后的主要因素(P＜0.01);性别、年龄、淋巴...     

Bone marrow involvement in patients with nodular lymphocyte predominant Hodgkin lymphoma

The significance of bone marrow involvement in patients with nodular lymphocyte predominant Hodgkin lymphoma is unknown. Of 275 patients diagnosed as lymphocyte predominant Hodgkin lymphoma at our institution (1983-2003), we identified 7 patients with purely nodular disease in the diagnostic lymph node biopsy specimen who also had bone marrow involvement. The latter was detected at the time of initial diagnosis in four patients, after one cycle of chemotherapy in one patient, and at relapse in two patients. There were six men and one woman with a median age of 37 years (range, 25-47 years). In all cases, the bone marrow was involved by large B cells, representing <10% of all cells, associated with a prominent T-cell and histiocytic background. All patients had laboratory, radiologic, and/or morphologic evidence of aggressive disease at the time of detection of bone marrow involvement. At last follow-up, four patients had died of their disease and three were alive following therapy. In conclusion, a small subset of patients in whom lymph node biopsy shows nodular lymphocyte predominant Hodgkin lymphoma with a purely nodular pattern also may have lymphoma in the bone marrow. Bone marrow involvement is associated with laboratory, radiologic, or morphologic evidence of aggressive disease and poor prognosis. Although the best terminology for these bone marrow lymphomas is uncertain, the aggressive clinical behavior of these neoplasms supports the need for intensive therapy.     

Hematologic malignant complications after transplantation

Post-transplant hemopathies are a serious complication of organ transplantation. They include several entities: non-hodgkin lymphoma, Hodgkin disease and myeloma. The pathophysiology, clinical and histological features, treatment and evolution of these diseases are different, but share some similarities. Among factors involved in lymphomagenesis, the role of Epstein Barr virus and immunosuppression are central. EBV primo-infection or reactivation together with a deep depression of T-cell immunity is at particular risk of lymphoma development. The clinical expression and outcome of lymphomas are varied. Assays for EBV replication quantification have been developed leading to immunosuppression decreasing and antiviral therapy when the replication increases. Treatment of post-transplant lymphoproliferations consists mainly in immunotherapy and chemotherapy. Hodgkin disease and myeloma are rare after transplantation; their management is close to the one of immunocompetent patients. The recurrence of myeloma, amyloidosis or light chain deposition disease seems frequent after transplantation and only patients with disappearance of monoclonal component should be proposed for transplantation. On the opposite, the risk of recurrence appears lower for Hodgkin disease; therefore the transplantation of patients with a history of Hodgkin disease looks possible.     

TRAF1 expression and c-Rel activation are useful adjuncts in distinguishing classical Hodgkin lymphoma from a subset of morphologically or immunophenotypically similar lymphomas

We demonstrate that the expression of TRAF1 and activated c-Rel, two proteins that function in signaling events downstream of activated CD30 in Reed-Sternberg cells, reliably distinguish classical Hodgkin lymphoma from anaplastic large cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and nonmediastinal diffuse large B-cell lymphoma. By immunohistochemistry, we found strong TRAF1 staining in 21 of 25 cases of classical Hodgkin lymphoma. In contrast, strong TRAF1 staining was present in only 1 of 17 cases of anaplastic large cell lymphoma, 0 of 15 cases of lymphocyte predominant Hodgkin lymphoma, and 2 of 36 cases of nonmediastinal diffuse large B-cell lymphoma. Nuclear staining for c-Rel, a pattern consistent with NFkappaB activation, was observed in the Reed-Sternberg cells in 23 of 25 cases of classical Hodgkin lymphoma but only in 1 of 15 cases of anaplastic large cell lymphoma and 3 of 15 cases of nodular lymphocyte predominant Hodgkin lymphoma. A heterogeneous pattern of subcellular c-Rel localization was found in nonmediastinal diffuse large B-cell lymphoma. Taken together, the combination of strong cytoplasmic TRAF1 expression and nuclear c-Rel was present in 80% of cases of classical Hodgkin lymphoma (n = 25) but in only 3% of cases of the other malignant lymphomas tested (n = 62). Thus, the differential expression patterns of downstream components in the CD30 signaling pathway may prove a useful adjunct in distinguishing cases of classical Hodgkin lymphoma from other malignant lymphomas in routine clinical practice.     

Aberrant expression of the dendritic cell marker TNFAIP2 by the malignant cells of Hodgkin lymphoma and primary mediastinal large B-cell lymphoma distinguishes these tumor types from morphologically and phenotypically similar lymphomas

Tumor necrosis factor-α-inducible protein-2 (TNFAIP2) is a protein upregulated in cultured cells treated with tumor necrosis factor α (TNF), but its expression in normal and neoplastic tissues remains largely unknown. Here, we use standard immunohistochemical techniques to demonstrate that TNFAIP2 is normally expressed by follicular dendritic cells, interdigitating dendritic cells, and macrophages but not by lymphoid cells in secondary lymphoid tissues. Consistent with this expression pattern, we found strong TNFAIP2 staining of tumor cells in 4 of 4 cases (100%) of follicular dendritic cell sarcoma and in 3 of 3 cases (100%) of histiocytic sarcoma. Although TNFAIP2 is not expressed by the small and intermediate-sized neoplastic B cells comprising follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, or marginal zone lymphoma, we observed strong TNFAIP2 staining of the large, neoplastic cells in 31 of 31 cases (100%) of classical Hodgkin lymphoma, in 12 of 12 cases (100%) of nodular lymphocyte-predominant Hodgkin lymphoma, and in 27 of 31 cases (87%) of primary mediastinal (thymic) large B-cell lymphoma. In contrast, TNFAIP2 was expressed by malignant cells in only 2 of 45 cases (4%) of diffuse large B-cell lymphoma, not otherwise specified, in 2 of 18 cases (11%) of Burkitt lymphoma, and in 1 of 19 cases (5%) of anaplastic large cell lymphoma. Further analysis indicates that TNFAIP2, as a single diagnostic marker, is more sensitive (sensitivity=87%) and specific (specificity=96%) than TRAF1, nuclear cRel, or CD23 for distinguishing the malignant B cells of primary mediastinal (thymic) large B-cell lymphoma from those of its morphologic and immunophenotypic mimic, diffuse large B-cell lymphoma, not otherwise specified. Thus, TNFAIP2 may serve as a useful new marker of dendritic and histiocytic sarcomas, the aberrant expression of which in the malignant cells of classical Hodgkin lymphoma and primary mediastinal (thymic) large B-cell lymphoma serves to distinguish these tumors from other large cell lymphomas in routine clinical practice.     

A Case of Age-Related Epstein–Barr Virus (EBV)-Associated B Cell Lymphoproliferative Disorder, so-called Polymorphous Subtype, of the Mandible, with a Review of the Literature

Epstein–Barr virus (EBV) is known to be associated with the development of lymphomas in immunocompromised patients. Recently, age-related immune impairment has been recognized as a predisposing factor in the development of EBV-driven lymphoproliferative disorders (LPDs) in elderly patients without any known immunodeficiency or prior lymphoma. In approximately 70 % of reported cases, the affected sites have been extranodal, such as the skin, lung, tonsil and stomach. However, age-related EBV-associated B cell (EBV + B cell) LPD is extremely rare in the oral cavity. Here we report a 71-year-old Japanese man who developed an EBV + B cell LPD resembling classical Hodgkin lymphoma (CHL)—so-called polymorphous subtype—of the mandible. Histopathologically, infiltration of large atypical lymphoid cells including Hodgkin or Reed-Sternberg-like cells into granulation tissue with marked necrosis was found in the mandibular bone. Immunohistochemical analysis revealed that the large atypical Hodgkin or Reed-Sternberg-like cells were CD3–, CD15–, CD20+, CD30+ and Epstein–Barr virus (EBV)-latent infection membrane protein-1 (LMP-1)+. In situ hybridization (ISH) demonstrated EBV-encoded small RNA (EBER) + in numerous Hodgkin or Reed-Sternberg-like cells. EBNA-2 was detected by polymerase chain reaction (PCR) using an extract from the formalin-fixed, paraffin-embedded specimen. To our knowledge, this is the first reported case of the polymorphous subtype of age-related EBV + B cell LPD affecting the mandible.     

Primary Small Cell Carcinoma of the Bladder: A Report of 25 Cases

Primary small cell carcinoma of the bladder is a rare condition with approximately 100 cases reported to date. An incidence of 0.7 percent small cell carcinoma was found in a total series of bladder tumors diagnosed in Western Sweden during a 2-year period. We describe 22 patients with primary small cell carcinoma followed to death or for at least 6 years. Three additional cases were diagnosed at autopsy. Of 18 patients with stages T2M0 to T4M0 cancer treated with locoregional therapy 5 (28 percent) had no evidence of disease after a median observation of 10 years (range 6 to 18) and 13 died of disease after 0.5 to 19 months (median 7.3). Two patients with metastatic disease were treated with systemic chemotherapy but died within 15 months. Two patients died shortly after the diagnostic biopsy. Our study and a review of the literature indicate that primary small cell carcinoma of the bladder is less aggressive than its pulmonary counterpart and that some patients can be cured by transurethral resection, or partial or radical cystectomy combined with radiotherapy.     

Prognosis of undifferentiated carcinoma and lymphoma of the thyroid

The experience with 126 patients with poorly differentiated thyroid carcinoma or lymphoma treated at the Lahey Clinic between 1931 and 1970 was reviewed. Undifferentiated thyroid tumors predominate in women and present late in life. While no giant cell tumors were found in patients less than forty years of age, small cell carcinoma and especially lymphoma can be seen earlier in life. Giant cell tumors were the most frequently found undifferentiated tumors in men while small cell types were commonest in women. These tumors involve extraglandular structures early; complete surgical removal is possible in only one third of the patients. Clinical course, survival, and biological behavior are closely related to the histologic type of the tumor. While patients who died of giant cell carcinoma had a median survival of three months and a five year survival of 8 per cent, patients with small cell carcinoma and lymphoma have a far better prognosis with a five year survival of 33 and 29 per cent, respectively. Differentiation of small cell carcinoma from lymphoma is often difficult but may be of no clinical significance at present.In view of our results we recommend: (1) total excision of tumor whenever possible, including limited neck dissection when this is required; (2) “debulking” procedures when feasible to aid in tracheostomy placement and use of radiotherapy and chemotherapy; (3) tracheostomy placement in the presence of any airway obstruction; (4) high dose external radiotherapy after operation or used as palliation in patients with nonresectable disease; (5) aggressive combination chemotherapy utilizing either adriamycin or actinomycin when palliation cannot be achieved by surgery and radiotherapy; and (6) thyroid hormone to avoid hypothyroidism, as the thyroid gland is usually functionally destroyed by the effects of invasive tumor and radiotherapy.     

Anticancer effect of sirolimus in renal allograft recipients with de novo malignancies

The inhibition of mTOR is a target for anticancer drugs in posttransplant malignancies. The influence of conversion to sirolimus after malignancy diagnosis was investigated on patient and renal allograft survivals. The 20 renal allograft recipients (4 women, 16 men) of ages 26 to 73 years (mean, 59 years) developed malignancies within 6 to 172 months (mean, 53 months) after transplantation. Three patients developed posttransplant lymphoproliferative disease (PTLD); four, Kaposi sarcoma, three, lung cancer; two, malignant melanoma; two, breast cancer; two, renal cell carcinoma; one, Merkel cell carcinoma; one, cutaneous T-cell lymphoma; one, larynx cancer; and one, gingival cancer. After tumor diagnosis, calcineurin inhibitors, azathioprine, or mycophenolate mofetil (MMF) were discontinued abruptly and sirolimus introduced (2 mg/d; target trough level, 4.0 to 8.0 ng/mL). Prednisone was maintained. The observation time of sirolimus therapy was 4 to 48 months (mean, 14 months). Two patients with PTLD (large B-cell lymphoma) and four with Kaposi sarcoma had full regressions. Eleven patients (larynx cancer, melanoma, breast cancer, T-cell lymphoma, renal cell carcinoma, Merkel cell carcinoma, and skin lymphoma) in addition to sirolimus therapy, underwent oncologic treatment, namely, surgery and/or chemotherapy. Six patients died from disseminated malignancy 4 to 9 months after conversion. One patient with T-cell lymphoma lost his graft; in the remaining patients, serum creatinine level was stable. In conclusion, Conversion to sirolimus resulted in regression of large B-cell lymphoma and Kaposi sarcoma. In patients with advanced or disseminated malignancy, the tumors progressed. Graft function was preserved after conversion to sirolimus.     

Carcinomas of the urinary bladder simulating malignant lymphoma. A report of five cases

We report five carcinomas of the urinary bladder, four of them transitional cell carcinomas and one undifferentiated carcinoma, with unusual features that have received little or no comment in the literature and may be the cause of diagnostic difficulty because of their possible confusion with malignant lymphoma. Four patients were male and one female. They ranged from 61 to 76 years of age. Three tumors from these patients had a prominent (2 cases) or massive (1 case) lymphoid infiltrate that partially obscured the invasive carcinoma in two cases and largely obscured it in the third case, which closely resembled a lymphoepithelioma. The diagnosis of malignant lymphoma was only excluded with confidence in the last case after thorough immunohistochemical study. The lymphoid infiltrate was composed of numerous T-cells (UCHL-1 and Leu 22 positive) and polytypic plasma cells with admixed eosinophils; occasional germinal centers were present in one case. The tumors were deeply invasive in two patients, one of whom is alive with no evidence of disease 4 years after treatment with chemotherapy and radiation therapy; the other two cases are too recent for meaningful follow-up. Two other transitional cell carcinomas had diffuse patterns that simulated lymphoma or plasmacytoma. Recognition of these patterns of vesical carcinoma is important in order to avoid the misdiagnosis of the very rare malignant lymphoma of the urinary bladder.     

Favorable response to combination treatment of cimetidine,cyclooxygenase‐2 inhibitor and renin‐angiotensin system inhibitor in metastatic renal cell carcinoma: Report of three cases

Abstract: We report three cases of metastatic renal cell carcinoma (RCC) in which combination treatment of cimetidine, cyclooxygenase‐2 inhibitor and renin‐angiotensin system inhibitor (angiotensin converting enzyme inhibitor or angiotensin II type 1 receptor antagonist) (CCA therapy) was effective. Case 1: A 47‐year‐old man who had a 12‐cm right renal tumor with multiple pulmonary and hepatic metastases refused cytokine therapy for economic reasons and received CCA therapy. All of the metastases showed partial remission, which continued for 12 months. Case 2: A 62‐year‐old man with multiple pulmonary and mediastinal lymph node metastases from clear cell RCC refractory to interferon‐α and interleukin‐2 started CCA therapy. Partial remission has been maintained for 16 months. Case 3: A 64‐year‐old man with pulmonary metastases from clear cell RCC discontinued interferon‐α treatment due to its side effects after six months and received CCA therapy. Pulmonary metastases showed partial remission for 31 months. The CCA therapy could be an alternative treatment for metastatic RCC patients unfit for cytokine therapy.     

Histological and immunohistological findings in lymphoepithelioid cell lymphoma (Lennert's lymphoma)

Four hundred and two cases considered or suspected to be lymphoepithelioid cell lymphoma (Lennert's lymphoma) were analyzed morphologically, immunohistochemically, and clinically. One hundred and eight of these cases, investigated in 180 biopsies, fulfilled the morphological and immunohistochemical criteria for lymphoepithelioid cell lymphoma and are herein reported. Cellular composition and histological structure are described in detail as a basis for discriminating Lennert's lymphoma from similar lymphomas with a high content of epithelioid cells (Hodgkin's disease, AILD type of T-cell lymphoma, lymphoplasmacytic lymphoma) and from inflammatory epithelioid cell reactions. Single typical Hodgkin cells were found in only 3.8% of biopsy specimens examined, and single typical Sternberg-Reed cells were found in only 2.2% of the biopsy specimens examined. Because these single Hodgkin and Sternberg-Reed cells were situated in a relatively monotonous lymphoid cellular pattern and because both these cells types also may occur in peripheral T-cell lymphomas, we include cases with such cells in the category of Lennert's lymphoma. Eight percent of the patients with lymphoepithelioid cell lymphoma showed transformation into a large-cell T-cell lymphoma without the prominent focal epithelioid cell component previously observed. Immunohistochemically, seven of the 69 biopsy specimens with detectable giant cells stained positively for the granulocyte-specific monoclonal antibody 3C4 (approximately CD15). Plasma cells were rare and always showed a polytypic immunoglobulin pattern. Lymphoepithelioid cell lymphoma, defined as a lymphoma of CD4+ T lymphocytes, marks the border between Hodgkin's disease and the non-Hodgkin's lymphomas. Today, absolute criteria for distinguishing between these two classes of lymphoma are lacking.     

CD20-negative T-cell-rich B-cell lymphoma as a progression of a nodular lymphocyte-predominant Hodgkin's lymphoma treated with rituximab: a molecular analysis using laser capture microdissection

Rituximab is a chimeric anti-CD20 monoclonal antibody. It has shown efficacy in patients with B-cell non-Hodgkin lymphoma and also in CD20-positive Hodgkin lymphoma. Recently, CD20-negative tumors have been described after Rituximab therapy. We report a 34-year-old man with a history of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), treated with different chemotherapy regimens, including anthracyclines and Rituximab. After 4 years in complete remission, he developed a CD20-negative T-cell-rich B-cell lymphoma (TCRBCL) presenting as multiple lung lesions. This case shows the difficulties in the diagnosis of CD20-negative lymphomas when the number of tumor cells is low and when they are found in a predominant T-cell context. Using anti-CD79a as a B-cell marker is mandatory to overcome the difficulties in identifying these tumors. Moreover, this case illustrates the usefulness of laser capture microdissection to obtain purified cell populations for molecular studies in lymphomas with relative paucity of tumor cells, as well as the need to analyze different IgH gene regions to decrease the rate of false-negative results in PCR clonality studies.     

Cutaneous manifestation of Kikuchi's histiocytic necrotizing lymphadenitis

A young man who presented with cervical Kikuchi's histiocytic necrotizing lymphadenitis later developed a cutaneous plaque lesion. Histologic study of the cutaneous lesion revealed dermal patchy infiltrates composed of large lymphoreticular cells and scattered cells resembling Hodgkin or Reed-Sternberg cells. This condition was initially mistaken for a large-cell lymphoma. But it was later discovered that the dermal cellular infiltrates were similar to that of the involved lymph node. Many of the large cells in the infiltrates were found to be histiocytes. Immunohistochemical study revealed that the cells resembling Hodgkin or Reed-Sternberg cells were activated fibroblasts. The presence of foamy histiocytes and the absence of neutrophils in the skin lesions were also similar to the involved lymph node. Cutaneous Kikuchi's disease may be mistaken for cutaneous lymphoma. Cutaneous involvement by Kikuchi's disease may also denote a worse clinical course.